Immunostimulatory compounds are compounds that can encourage cytokine production and hence macrophage production, all being part of a normal immune system reaction observed in organisms. The main effects of immunostimulatory compounds result in the migration of macrophages to an inflamed area and an increase in (already existing) macrophage activity.
Inflammation relating to immune stimulation is often considered a negative reaction or a reaction to be avoided, particularly in the context of wound healing—i.e. why would you further inflame an already inflamed wound? The inventors have found that inflammation at least in the wound healing context is in fact beneficial for most wound applications contrary to that expected. As well as and distinct to anti-microbial effects, certain types of so-called ‘active’ honey appear to prime or kick start the immune system into action, a characteristic not uncommon in some contexts with positive outcomes e.g. to address chronic or recalcitrant infections where the natural wound healing process has stalled or alternatively, to prompt a reaction such as that observed when probiotic bacteria are introduced to the gut.
Many studies have also been produced showing how humans and animals react when their immune system is primed or kick started into action. For example, mice primed via an immune stimulatory challenge often survive another microbial challenge better than mice not primed. Many products utilising this priming function are administered orally, for example as lozenges, elixirs, sprays, tablets and capsules.
Arabinogalactan (AG) is a biopolymer consisting of arabinose and galactose monosaccharides. Two classes exist in nature being plant arabinogalactans and microbial arabinogalactans. In plants, AG is a major constituent of many gums including gum arabic, gum gutti and so on. AG is also found in Echinacea and other plant matter, typically in the amount of 0.1% weight or 100 μg/ml-200 μg/ml.
AG may be attached to proteins and the resulting arabinogalactan protein (AGP) functions as a signalling molecule between cells.
Honey derived AGP compounds appear to have immunostimulatory effects not seen in other types of AGP compounds. The activity of honey derived AGPs are described for example in WO2011/139168 (incorporated herein by reference), and the use of such compounds in a purified or concentrated form is also described illustrating the importance and commercial advantages of the activity of AGPs.
By contrast to the above, gum arabic-AGP and coffee-AGP have insignificant immunostimulatory effects, a finding somewhat surprising but which however illustrates how the specific proteins present in honey clearly have a very different effect on AGP activity.
Apisimin is one of three key functional proteins naturally found in royal jelly.
Royal jelly is a principal food of the honeybee queen and young female larvae. It is secreted from the hypopharyngeal and mandibular glands of honeybees. Royal jelly is often taken as a supplement for various nutritional benefits. Chemical analysis of royal jelly has shown that royal jelly from honey bees (Apis species) consists mainly of proteins (12-15%) which constitute about 50% of its dry mass. Royal jelly also includes carbohydrates (10-16%), lipids (3-6%), vitamins and free amino acids, together with several bioactive substances. Besides apisimin, the other two key functional peptides are apalbumin and royalisin.
A number of papers exist in regard to apalbumin and royalisin, which teach about the activity of these peptides and their make-up as well as processes of extraction and recombinant manufacture.
Apisimin by contrast is relatively poorly researched although one paper, Bilikova et al FEBS Letters 528 (2002) 125-129 describes apisimin as being a new serine-valine rich peptide and also describes purification and molecular characterisation methods. Apisimin is described as being a 5.5 kDa sized molecule having 54 amino acids. The paper gives nucleotide and encoded amino acid sequences for apisimin.
It should be appreciated from the above that it would be useful to have improved immunostimulatory compositions and methods of manufacture and/or at least provide the public with a useful choice.
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